This invention relates to an apparatus for separating substances through a membrane. The term "separation" applied herein means a process of dialysis by which the substances contained in the first fluid are transferred to the second fluid through said membrane, a process of permeation of the first fluid itself into the second fluid in which the transfer of substances in the first fluid through the membranes is suppressed, or a process of filtration of substances present in the first fluid through the membrane.
Thus, in particular, this invention relates to an apparatus applicable to a wide variety of processes requiring a high ratio of the effectively working surface area of the membrane against the volume of the apparatus, such as an artificial lung for exchanging carbonic acid gas for oxygen through the membrane, an inverse permeation apparatus for purification and desalting of water, an artificial kidney for blood purification, or an ascitic treatment apparatus for condensing ascites collected in the abdominal cavity.
Still further, this invention concerns an apparatus for removing impurities and excessive water content from the blood by extracorporeal hemodialysis or hemo-filtration, having a very large effective membrane surface area within a small unit, requiring only a small priming quantity of blood, and being portable during the use thereof.
In the field of artificial kidneys, a trial application of the principle of dialysis or ultra-filtration is under way for purification of blood by hemodialysis or hemo-filtration. An artificial kidney to which the principle of dialysis is applied has already been in practical use. Purification of blood by dialysis results from a concentration gradient arising across the semipermeable membrane. That is, impurities present in the blood permeate from blood into dialysate through the membrane at higher speed than that of permeation in the inverse direction and, as a result, an effective transfer of impurities is achieved.
The microscopic holes of the semipermeable membrane used for hemodialysis are large enough to allow relatively small molecules of impurity to pass therethrough but not blood cells and protein which are large in molecular size. Sugar and various kinds of salt which are an indespensable constituent for blood are so small in size that they can pass through these holes, however, they are prevented from being removed from the blood if contained in the dialysis, too, at an equal degree of concentration to that in the blood. Excessive water content is also removed from the blood by ultrafiltration. In this case, water content is driven out from the blood through the holes of semipermeable membrane by generating a pressure gradient across the membrane, rendering the pressure on the side of blood slightly higher than that on the side of dialysate.
An artificial kidney to which the principle of ultrafiltration is applied is in review at the present time. Purification of blood by means of filtration is discussed in connection with four major methods as follows:
(1) A method to remove impurities in the blood and the filtered blood plasma including low-molecular-weight substances through the membrane and return blood corpuscle components and condensed blood including high-molecular-weight substances to the human body;
(2) A method to separate blood into a group of blood corpuscle components and condensed blood including high-molecular-weight substances and the other group of impurities and filtered blood plasma including low-molecular-weight substances, and return the filtered blood plasma in the form of a mixture with condensed blood to the human body after removing toxicity, adjusting electrolyte, and removing excessive water content;
(3) A method to dilute blood with substitution fluid, filter the diluted blood in quantity equal to the increment due to dilution through the membrane, remove filtered blood plasma including impurities and low-molecular-weight substances, and return the remaining blood to the human body;
(4) A method to filter the blood in two steps using two kinds of membranes differing from each other in diameter of the hole, pass the corpuscles filtered through the membrane in the first step through active carbon adsorbent, filter the low-molecular-weight substance having a value on the order of several hundreds through the membrane in the second step, and, after removing toxicity, adjusting electrolyte, and removing excessive water content, return the filtered corpuscles in the form of a mixture with condensed substitution fluid to the human body.
However, the dialysis type artificial kidney or the filtration type one hitherto used have drawbacks such as requiring a large quantity of blood due to the priming volume thereof still remaining considerably large, incurring some quantity of blood loss for the same reason as above, requiring an external blood pump for coping with resistance of the fluid path, and necessitating the skilled technical personnel for operation control over the artificial kidney and an attendance of a physician.
Accordingly, efforts for developing an artificial kidney are being directed in these days toward miniaturization of the apparatus without functional decline for minimizing the priming volume and elimination of the need for an external blood pump.
As a new development in this field, in U.S. Pat. Nos. 3,522,885 and 3,565,258, there is disclosed a small-sized hemodialyzer in which a large number of parallelly disposed membrane tubes made of regenerated cellulose, both ends of all tubes being connected with each other with epoxy resin so as to provide a common opening communicating with every tube, are contained in the plastic case and the membrane support members are arranged between or within said parallelly disposed tubes in large number as said above. Also, in U.S. Pat. No. 3,788,482, a small-sized hemodialyzer is disclosed wherein membrane support members are inserted into pleats on one side of a sheet-like membrane made of regenerated cellulose and folded in the form of closely spaced pleats, each end of said membrane being sealingly embedded into the plastic material constituting a part of the case.
These hemodialyzers are considerably smaller in size because of the use of thin nonwoven meshes as membrane support members, requiring no external blood pump and being disposable after use.
However, a hemodialyzer using nonwoven meshes as membrane support members has various functional disadvantages as follows:
(1) There is a tendency to make bubbles stay at the meshes of the membrane support member. As will be described later the, staying of bubbles is a large factor in causing functional decline of dialysis;
(2) When the membrane support member is made thinner for miniaturization of the apparatus, filaments composing the nonwoven mesh are obliged to be made fine and deform in the direction from the blood side to the dialysate side due to the blood pressure. As a result, a deviation in the flow of blood and dialysate, an increase in resistance of fluid path, and, in addition, deviation in the supply quantity of blood are caused.
The hemodialyzer using nonwoven meshes as membrane support members can be made small in size as mentioned above and can reduce priming volume but, as a result, is obliged to sacrifice dialytic function. Therefore, it is preferrable to avoid the use of nonwoven mesh as a membrane support member for providing a hemodialyzer small in size with high performance.
On the other hand, U.S. Pat. Nos. 3,841,491 and 3,837,496 disclose a hemodialyzer using a membrane support plate minutely molded as the membrane support member. The structure of this apparatus includes a large number of support plates elaborately designed, mutually connected, and arranged so that the flat surfaces thereof are put into contact relation with each other through a pair of interposed membranes which form a fluid path therebetween. The assembly composed of support plates and membranes is provided with a dialysate manifold hole extending throughout the assembly and fitted with dialysate distributing discs for forcing the support plate towards the adjacent membrane, as well as a blood manifold hole extending throughout the assembly and fitted with blood distributing discs for forcing the support plate to the adjacent membrane.
In such a hemodialyzer, minutely molded membrane supporting plastic plates are used. Since elaborate fluid paths for dialysate and blood are provided on either surface of this support plate, these fluids can flow smoothly through respective paths. As compared with the hemodialyzer using said non-woven meshes, this apparatus is excellent in performance. Hence, for promoting dialytic function, the use of a molded support plate is recommended. As a method to mold such an elaborately designed support plate on a mass-scale, injection molding has been employed. However, it is technically difficult to mold such an elaborately designed support plate as thin as 1.2 mm or less by injection molding, and particularly more difficult in the case of a thickness of 0.5 mm or less. Because of such circumstances, the support plate molded by injection molding and used for the hemodialyzers generally sold on the market is so thick, ranging from 2 to 5 mm, that these hemodialyzers containing many pairs of membranes in stack are bulky, and posses such drawbacks as large priming volume and difficulty in handling in the hospital.
An idea to minimize the size of a hemodialyzer by molding an elaborately designed thin support plate with the application of a method other than injection molding may easily occur. However, it has been found that there arise many problems which are unforeseen from the hemodialyzers using conventional support plates and which bring about functional decline when only the thickness of support plate in a conventional structure is reduced without any other modification. The most important problem, among others, is that the thinner the support plate is made, the more the bubbles stay in the dialysate path.
The reason why the number of staying bubbles increases with the reduction of thickness of the membrane support plate is comprehended as follows:
The bubbles are subjected to the surface tension of ambient fluid acting to maintain the globular shape of the bubbles and resist deformation. It will be obvious that such resistance becomes larger in proportion to decrease in the size of bubble and increase in the degree of deformation. Accordingly, when the membrane support plate is made thinner, that is, the cross section area of fluid path is smaller, finer bubbles are generated and resist deformation more. In the conventional membrane support plate, for example, the section area of fluid path is small at the juncture where the slit-like opening for a dialysate distributing header is connected with the fluid path of dialysate formed between the support plate and the adjacent membrane. Bubbles contained in the dialysate can not easily be discharged from the slit-like opening to the fluid path of the dialysate along the fluid flow unless divided into two parts in the direction of thickness or deformed to such an extent as to be halved or less. In a comparatively thick support plate of conventional type, the number of staying bubbles is small since small bubbles pass through said juncture and large ones incapable of passing therethrough by remaining unchanged in size are easily deformed by fluid flow owing to less resistance to deformation, thereby, passing therethrough. In contrast with this, when a support plate is made thinner, small and undeformable bubbles generate and show a high degree of resistance to the connecting portion abruptly changed in configuration, becoming incapable of passing through said portion and staying at the slit-like opening. The nonwoven mesh sheet has an abrupt change in section area at the connecting portion of individual meshes where the rate of change in area from the connecting portion to the mesh portion numbers one half or less and, therefore, bubbles stay inevitably. In the molded support members, too, there is a fear that bubbles stay at not only the slit-like opening but the membrane support portion in the central zone of the support plate on account of swelling of the membrane during use. Swelling of the membrane must be taken into full consideration with respect to the projections and arrangement thereof for forming the membrane support zone.
The reasons for preventing bubbles from staying in the artificial kidney is as follows:
(1) Fluid does not flow where bubbles are present in the fluid path, as contact of fluid with the membrane is interrupted and as a result the effective area of the membrane is reduced;
(2) Clogging of bubble in the fluid path increases the resistance of the fluid path;
(3) Flow of fluid deviates as the fluid does not flow where bubbles are present; and,
(4) There is a risk that the fluid forming bubbles diffuse into the blood through the membrane, which leads to blood coagulation due to contact of blood with air.
When thus viewed, it is important to develop a construction of the membrane support plate in which no bubbles stay, that is, no abrupt change in section area is produced in the fluid path, for providing a small-sized hemodialyzer of high performance of dialysis using thin plates as membrane support members. Similarly, it is also important to reduce blood priming volume by miniaturizing the hemodialyzer and, on the other hand, to raise the efficiency thereof by enlarging the interfacial area of the membrane between the blood and the dialysate.
Another object of the development of the artificial kidney is to provide an apparatus portable during use and continuously operable, requiring only periodic replacement. The patient may have no other need than a single replacement per week or month of such an artificial kidney as above which is operable while attached to the body of the patient who leads daily normal life, and he may be released from the inconvenience of having to undergo blood purifying treatment at fixed intervals. Further, a continuously operable artificial kidney will help prevent accumulation of toxic materials in blood, thanks to which the patient will gradually recover his health.
An artificial kidney of such a kind which is portable and continuously operable can be developed on the basis of research into the following three points:
(1) Establishment of a method for completely preventing blood coagulation in the apparatus;
(2) Finding a method for cleansing dialysate so as to minimize a required quantity of dialysate for operation, or a method for treating the discharge filtration liquid when using the filtration type artificial kidney; and,
(3) Development of an apparatus provided with a working surface of the largest possible area in the smallest possible volume for obtaining effective dialysis as well as for enabling the patient to conveniently carry the apparatus during his daily activities.
The first two of the above problems are now on the way of solution, and the last one for providing a sufficient area in the smallest volume is considered soluble by utilizing the embodiment of this invention. Thus, this invention is applicable to an artificial kidney that is portable and continuously operable.